Which antidepressant is known to be associated with weight gain?

• A. Sertraline
• B. Mirtazapine
• C. Fluoxetine
• D. Venlafaxine

Answer: (B)

Weight gain is a known issue with certain antidepressants, due to how they affect appetite and metabolism. Mirtazapine stands out for this because of its pharmacology as a noradrenergic and specific serotonergic antidepressant (NaSSA). It blocks presynaptic alpha-2 receptors, which increases norepinephrine and serotonin release, and it also antagonizes 5-HT2 and 5-HT3 receptors. But its strongest weight-related effect comes from strong antihistaminic (H1) activity, which tends to increase appetite and cause sedation. Clinically, many patients experience increased appetite and significant weight gain in the weeks to months after starting it. This makes weight gain a particularly notable and expected side effect with this medication.

In contrast, the other options are less commonly associated with weight gain. Sertraline tends to be weight-neutral or cause only modest gain over time; fluoxetine is often linked with weight loss early in treatment and less weight gain overall; venlafaxine can cause variable weight changes but is not as strongly associated with weight gain as mirtazapine.